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Learn MorePancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with overall five-year survival of 8%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC, however subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumor biology. It is clear that hyperactivation of MYC generates dependencies, which can be exploited therapeutically. To find MYC-associated dependency we analyzed human PDAC expression dataset. We observed that MYC is connected to the sumoylation machinery in PDAC. Components of the SUMO pathway mark a PDAC subtype with worse prognosis and we provide evidence that PDACs with a MYChigh/SUMOhigh phenotype respond to a novel SUMO inhibitor, offering the opportunity to develop novel stratified PDAC therapies SOURCE: Matthias WirthGeb. 14.79 Uniklinikum Düsseldorf
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